Epcoritamab and Lenalidomide in Treating Patients With Refractory or Relapsed Immunodeficiency-Related Large B-Cell Lymphoma

NCT06723457 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: NU 24H07NCI-2024-09812STU00222751P30CA060553
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well the combination of epcoritamab and lenalidomide work in treating patients with immunodeficiency-related large B-cell lymphoma that does not respond to treatment (refractory) or that has come back after a period of improvement (relapsed). Epcoritamab is an immunotherapy that engages T-cells in the immune system to help redirect their killing effects against lymphoma cells. Lenalidomide can modulate the immune system to enhance killing effects of lymphoma by the immune system as well. Giving patients a combination of epcoritamab and lenalidomide may work better in treating refractory or relapsed immunodeficiency-related large B-cell lymphoma.

Conditions

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Polymorphic Post-Transplant Lymphoproliferative Disorder; Refractory B-Cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Best response of complete response (CR) rate

  The combination of epcoritamab-lenalidomide in chemotherapy ineligible patients with primary refractory or relapsed immunodeficiency-related large B-cell lymphoma, indicated by the number of patients with CR as best response (using the Lugano Criteria) divided by the total number of patients who have received 1 dose of combination therapy and have had response assessment by radiographic imaging by 6 months from start of therapy. The six-month best response of CR rate will be estimated by the number of patients with complete response divided by the total number of patients who have received 1 dose of combination therapy and have had response assessment by radiographic imaging by 6 months from start of therapy. This estimation will be compared with the historical control 35% by Exact Test of one proportion. At the same time, the Blyth-Still-Casella exact binomial 95% confidence interval of this CR rate will be calculated with adjustment.

  At 6 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  From the initiation of trial therapy until: the response has been confirmed, the subject experiences disease progression, initiates subsequent anti-cancer therapy, or completes study participation. This will be assessed at 3, 6, 12, 18, and 24 months.

• Duration of response (DOR)

  The elapses between the day of first documented response to trial therapy (CR or PR, whichever is recorded firstly) and subsequent disease progression, assessed at 6, 12, 18, and 24 months

• Progression-free survival (PFS)

  From initiation of trial therapy to PD per the 2014 Lugano Criteria, other documented clinical or radiographical progression per physician judgement, or death due to disease, assessed at 12, 18, and 24 months

• Overall survival (OS)

  The time that elapses between initiation of trial therapy and the date of death from any cause for all evaluable patients, assessed at 12, 18, or 24 months.

• Incidence of adverse events

  Up to 24 months

Study Arms (1)

Treatment (epcoritamab, lenalidomide)

EXPERIMENTAL

Patients receive epcoritamab SC weekly during cycle 1 and on days 1, 8, 15, and 22 of cycles 2-3, and day 1 of cycles 4-12. Patients also receive lenalidomide PO on days 1-21 of each cycle. Cycles repeat every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT and collection of blood samples throughout the study and may undergo MRI during screening.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Epcoritamab; Drug: Lenalidomide; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (epcoritamab, lenalidomide)

Computed Tomography PROCEDURE

Undergo PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (epcoritamab, lenalidomide)

Epcoritamab BIOLOGICAL

Given SC

Also known as: Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly, GEN 3013, GEN-3013, GEN3013, Tepkinly

Treatment (epcoritamab, lenalidomide)

Lenalidomide DRUG

Given PO

Also known as: CC 5013, CC-5013, CC5013, CDC 501, Revlimid

Treatment (epcoritamab, lenalidomide)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (epcoritamab, lenalidomide)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (epcoritamab, lenalidomide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a pathologically confirmed diagnosis of immunodeficiency-related large B-cell lymphoma as defined by the 5th Edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors 2022 in addition to any of the following:
• Lymphomas arising in immune deficiency which encompass monomorphic post-transplant lymphoproliferative disorder (PTLD) OR
• Polymorphic B-cell lymphoproliferative disorder arising in the setting of immunodeficiency and/or immune dysregulation as seen in 1 or more of the following settings:
• Underlying autoimmune disease
• Iatrogenic or therapy-related immunosuppression
• Conditions arising from inborn errors of immunity
• Immune senescence as seen in patients aged ≥80 years or those ≥ 65 years with CD4 count \< 500 cells/mm\^3
• Epstein-Barr virus (EBV) infection as demonstrated by EBV positivity in the tumor cells
• Patients must have measurable disease (≥ 1 measurable nodal lesion \[long axis \> 1.5 cm\] or ≥ 1 measurable extra-nodal lesion \[long axis \> 1.0 cm\] on CT scan or MRI) per Lugano criteria
• Note; Patients with hepatomegaly /organomegaly deemed to be related to disease will also be eligible if not meeting strict Lugano criteria
• Patients must meet one disease status as follows AND deemed ineligible for chimeric antigen receptor T-cell (CAR-T):
• Primary refractoriness defined as a partial response or less on interim PET-CT during therapy with frontline chemo-immunotherapy (containing anti-CD20 monoclonal antibody)
• Primary refractoriness defined as a partial response or less on interim PET-CT during therapy with rituximab (or any other anti-CD20 monoclonal antibody) monotherapy AND deemed ineligible for escalation to chemotherapy
• Relapse after achieving a complete response with ≥ 1 prior systemic therapy (including CART)
• Patients must be aged ≥ 18 years

You may not qualify if:

• Patients who have received any prior therapy with a bispecific T-cell engager targeting CD3 and CD20
• Patients who have received chemotherapy and/or other antineoplastic agents (except CD20- targeting monoclonal antibodies, steroids and/or radiation) within 1 week or 5 half-lives (whichever is shorter) prior to registration
• Patients who have undergone autologous stem cell transplant (ASCT) within 100 days of registration
• Patients who have undergone CAR-T therapy with refractoriness or relapse within 30 days of registration
• Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab and/or lenalidomide
• Patients with human immunodeficiency virus (HIV) with detectable viral load and CD4 count ≤350 cells/mm3 \& not on treatment for more than 1 year
• Patients with evidence of active disease in the central nervous system (CNS) defined as either the presence of active lesions on MRI or cerebrospinal fluid (CSF) studies obtained within 4 weeks prior to registration or progressive neurological decline, attributable to CNS disease
• Patients who have a seizure disorder that is not controlled (requiring anti-epileptic therapy AND with seizure within 12 months of registration)
• Patients who have had major surgery within 4 weeks prior to registration
• Patients who have clinically significant cardiac disease include the following:
• Myocardial infarction or stroke within 6 months prior to enrollment,
• OR the following conditions within 6 months prior to enrollment: unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV), uncontrolled cardiac arrhythmia, and uncontrolled hypertension),
• OR Other clinically significant electrocardiogram (ECG) abnormalities within 6 months prior to enrollment unless deemed stable and appropriately treated
• OR Left ventricular ejection fraction \< 45% for Echocardiogram
• Patients who are unable to swallow, retain and absorb oral tablet/gel/capsules

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Specimen Handling; Lenalidomide; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Reem Karmali, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2024
• First Posted: December 9, 2024
• Study Start: July 25, 2025
• Primary Completion (Estimated): February 18, 2027
• Study Completion (Estimated): February 18, 2029
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (1)